rs12680687

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002485.5(NBN):​c.2185-2085C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,882 control chromosomes in the GnomAD database, including 6,881 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 6881 hom., cov: 31)

Consequence

NBN
NM_002485.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.361
Variant links:
Genes affected
NBN (HGNC:7652): (nibrin) Mutations in this gene are associated with Nijmegen breakage syndrome, an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. The encoded protein is a member of the MRE11/RAD50 double-strand break repair complex which consists of 5 proteins. This gene product is thought to be involved in DNA double-strand break repair and DNA damage-induced checkpoint activation. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NBNNM_002485.5 linkuse as main transcriptc.2185-2085C>A intron_variant ENST00000265433.8 NP_002476.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NBNENST00000265433.8 linkuse as main transcriptc.2185-2085C>A intron_variant 1 NM_002485.5 ENSP00000265433 P1

Frequencies

GnomAD3 genomes
AF:
0.299
AC:
45413
AN:
151764
Hom.:
6869
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.340
Gnomad AMI
AF:
0.218
Gnomad AMR
AF:
0.320
Gnomad ASJ
AF:
0.225
Gnomad EAS
AF:
0.381
Gnomad SAS
AF:
0.286
Gnomad FIN
AF:
0.269
Gnomad MID
AF:
0.245
Gnomad NFE
AF:
0.275
Gnomad OTH
AF:
0.283
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.299
AC:
45459
AN:
151882
Hom.:
6881
Cov.:
31
AF XY:
0.300
AC XY:
22282
AN XY:
74240
show subpopulations
Gnomad4 AFR
AF:
0.340
Gnomad4 AMR
AF:
0.320
Gnomad4 ASJ
AF:
0.225
Gnomad4 EAS
AF:
0.381
Gnomad4 SAS
AF:
0.288
Gnomad4 FIN
AF:
0.269
Gnomad4 NFE
AF:
0.275
Gnomad4 OTH
AF:
0.281
Alfa
AF:
0.282
Hom.:
2217
Bravo
AF:
0.304
Asia WGS
AF:
0.305
AC:
1061
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
2.2
DANN
Benign
0.76
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12680687; hg19: chr8-90951388; API